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Metabolites
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Pharmaceutical Sciences and Metabolism
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Pharmaceutical Sciences and Metabolism

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Pharmacology and Drug Metabolism".

Deadline for manuscript submissions: closed (15 March 2021) | Viewed by 10373

Special Issue Editor

Prof. Valérie Sautou

E-Mail Website
Guest Editor
Department of Pharmacy, Université Clermont Auvergne, Clermont-Ferrand, France
Interests: content-container interactions; medical devices and packagings; leachables; degradation products and metabolites

Special Issue Information

Dear Colleagues,

During a drug development, the data concerning the metabolism of the active ingredient are essential for its marketing and are the subject of extensive pharmacokinetic studies. However, these cannot be exhaustive because the knowledge evolves according to the conditions of clinical use. The conditions of a drug administration can have a significant impact on the metabolism of the active ingredient (s), in particular during polymedication, food-based supplements, phytotherapy products, …. These co-administrations can lead to interactions likely to have an impact on the therapeutic management of patients. In addition, packagings and medical devices for administering drugs can release substances which may have toxic effects after human metabolism.

This Special Issue of Metabolites will publish reviews and original articles covering the latest on these subjects:

  • Impact of drug-drug interactions, drug-food supplement interactions; drug-phytotherapy interactions on the metabolism of drugs and therapeutic management (efficacy and toxicity)
  • Metabolism and toxicity of compounds released from packaging materials and medical drug delivery devices (toxicokinetics and biomonitoring studies)

Prof. Valérie Sautou
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Drug metabolism
  • Drug-drug interactions
  • Drug-food supplement interactions
  • Drug-phytotherapy products interactions
  • Leachables’metabolites

Published Papers (3 papers)

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Research

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16 pages, 2204 KiB  
Article
Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management
by Lise Bernard, Yassine Bouattour, Morgane Masse, Benoît Boeuf, Bertrand Decaudin, Stéphanie Genay, Céline Lambert, Emmanuel Moreau, Bruno Pereira, Jérémy Pinguet, Damien Richard, Valérie Sautou and for the ARMED Study Group
Metabolites 2021, 11(4), 252; https://doi.org/10.3390/metabo11040252 - 19 Apr 2021
Cited by 7 | Viewed by 2176
Abstract
Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates’ exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation [...] Read more.
Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates’ exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers’ exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used for care management, and (2) by measuring the patients’ urinary levels of each plasticizers’ metabolites. 104 neonates were enrolled. They were exposed to di-isononylphthalate (DINP), especially via transfusion and infusion MD, and to DEHP via ECMO (Extra Corporeal Membrane Oxygenation) and respiratory assistance MD. Mean exposure doses exceeded the derived no-effect level of DINP and DEHP by a 10-fold and a 1000-fold factor. No PVC MD were plasticized with di-isononylcyclohexane-1,2-dicarboxylate (DINCH). High urinary concentrations of DEHP metabolites were directly correlated with DEHP exposure through ECMO MD. Urinary concentrations of DINP metabolites in transfused patients were also high. DINCH metabolites were found in urine, suggesting another route of exposure. Neonates in NICU are considerably exposed to plasticizers, with magnitudes varying with the type of MD used. The high exposure to DEHP and DINP leads to a risk of their metabolites’ toxicity. Full article
(This article belongs to the Special Issue Pharmaceutical Sciences and Metabolism)
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10 pages, 5287 KiB  
Article
Does DDI-Predictor Help Pharmacists to Detect Drug-Drug Interactions and Resolve Medication Issues More Effectively?
by Fanny Moreau, Nicolas Simon, Julia Walther, Mathilde Dambrine, Gaetan Kosmalski, Stéphanie Genay, Maxime Perez, Dominique Lecoutre, Stéphanie Belaiche, Chloé Rousselière, Michel Tod, Bertrand Décaudin and Pascal Odou
Metabolites 2021, 11(3), 173; https://doi.org/10.3390/metabo11030173 - 17 Mar 2021
Cited by 9 | Viewed by 2760
Abstract
The characterization of drug-drug interactions (DDIs) may require the use of several different tools, such as the thesaurus issued by our national health agency (i.e., ANSM), the metabolic pathways table from the Geneva University Hospital (GUH), and DDI-Predictor (DDI-P). We sought to (i) [...] Read more.
The characterization of drug-drug interactions (DDIs) may require the use of several different tools, such as the thesaurus issued by our national health agency (i.e., ANSM), the metabolic pathways table from the Geneva University Hospital (GUH), and DDI-Predictor (DDI-P). We sought to (i) compare the three tools’ respective abilities to detect DDIs in routine clinical practice and (ii) measure the pharmacist intervention rate (PIR) and physician acceptance rate (PAR) associated with the use of DDI-P. The three tools’ respective DDI detection rates (in %) were measured. The PIRs and PARs were compared by using the area under the curve ratio given by DDI-P (RAUC) and applying a chi-squared test. The DDI detection rates differed significantly: 40.0%, 76.5%, and 85.2% for ANSM (The National Agency for the Safety of Medicines and Health Products), GUH and DDI-P, respectively (p < 0.0001). The PIR differed significantly according to the DDI-P’s RAUC: 90.0%, 44.2% and 75.0% for RAUC ≤ 0.5; RAUC 0.5–2 and RAUC > 2, respectively (p < 0.001). The overall PAR was 85.1% and did not appear to depend on the RAUC category (p = 0.729). Our results showed that more pharmacist interventions were issued when details of the strength of the DDI were available. The three tools can be used in a complementary manner, with a view to refining medication adjustments. Full article
(This article belongs to the Special Issue Pharmaceutical Sciences and Metabolism)
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Review

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16 pages, 2140 KiB  
Review
Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches
by Yaru Peng, Zeneng Cheng and Feifan Xie
Metabolites 2021, 11(2), 75; https://doi.org/10.3390/metabo11020075 - 27 Jan 2021
Cited by 29 | Viewed by 4898
Abstract
Pharmacokinetic drug–drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect the drug efficacy [...] Read more.
Pharmacokinetic drug–drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect the drug efficacy and safety in patients. Enzyme-mediated DDIs are of primary concern, while the transporter-mediated DDIs are less understood but also important. In this review, we presented an overview of the different mechanisms leading to DDIs, the in vitro experimental tools for capturing the factors affecting DDIs, and in silico methods for quantitative predictions of DDIs. We also emphasized the power and strategy of physiologically based pharmacokinetic (PBPK) models for the assessment of DDIs, which can integrate relevant in vitro data to simulate potential drug interaction in vivo. Lastly, we pointed out the future directions and challenges for the evaluation of pharmacokinetic DDIs. Full article
(This article belongs to the Special Issue Pharmaceutical Sciences and Metabolism)
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